Insulin-like growth factor receptor-1 expression predicts postoperative recurrence in adenocarcinoma of the lung

Abstract

Abstract. Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers exist for either selecting appropriate candidates or for predicting clinical recurrence. The purpose of the present study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGFR1) in lung adenocarcinoma. Tumor specimens were collected from 182 patients who underwent a complete resection for adenocarcinoma of the lung. The expression of IGFR1 was evaluated by immunohistochemistry. The genetic status of the epidermal growth factor receptor (EGFR) and K-ras genes was also investigated by PCR-based analyses. Immunohistochemistry and real-time PCR assays were used to evaluate the MET gene association with tyrosine phosphorylation and hepatocyte growth factor (HGF) status, and amplification, respectively. Positive expression of IGFR1 was detected in 43 (23.6%) of the 182 cases. A positive IGFR1 expression was also identified in 12 (42.9%) and 31 (20.1%) of the patients with and without recurrence, respectively (p=0.009). Logistic regression models indicated that positive staining for IGFR1 expression was an independent factor associated with tumor recurrence. IGFR1 expression was associated with a poorer disease-free survival (DFS). Multivariate analysis demonstrated positive IGFR1 expression to be independently associated with an increased risk for poor DFS. The tumors appearing positive for IGFR1 were more frequent among those with K-ras mutations when compared with the wild-type group. IGFR1 expression was associated with reduced DFS correlating with postoperative recurrence. Therefore, the expression status of IGFR1 can be a candidate surrogate marker to select patients who may benefit from adjuvant chemotherapy. IntroductionLung cancer is the leading cause of cancer-related death in the world (1). The incidence of adenocarcinoma, one of the major histological subtypes of non-small cell lung cancer (NSCLC), is increasing (2). The prognosis is dismal as the 5-year survival is only approximately 50%, even in patients who achieve complete surgical resection (3). This suggests that occult metastases are present at the time of surgical intervention. As a consequence, adjuvant chemotherapy is required (4). However, the 5-year survival rate of patients with resected stage IB NSCLC is 74% without adjuvant chemotherapy, suggesting that not all patients require chemotherapy after a complete resection (5). Therefore, it is necessary to identify patients who may benefit the most from post-operative adjuvant chemotherapy to, not only precisely select the patients who require additional treatment, but also to prevent the occurrence of adverse events in patients who do not require treatment (4). Therefore, it is important to evaluate the biological and molecular characteristics of lung adenocarcinoma to identify the factors related to recurrence following surgery. However, there are currently no useful markers that predict clinical recurrence.Insulin-like growth fa...

Epidermal growth factor receptor (EGFR), HER2 and insulin‐like growth factor‐1 receptor (IGF‐1R) status in ovarian adult granulosa cell tumours

“…A member of the receptor tyrosine kinase family, it is activated by IGF‐I or IGF‐II, with phosphorylation of tyrosine residues and activation of two signalling pathways, namely Ras/Raf and phosphatidylinositol 3‐kinase/AKT. Interestingly, in our study we found IGF‐1R to be highly expressed in 41% of AGCTs, a similar rate to what has been found in breast cancer . This raises the possibility that anti‐IGF‐1R agents have a potential role in the management of AGCTs.…”

“…IGF‐1R is a transmembrane heterotetrameric protein which plays a role in the development of cancer by promoting oncogenic transformation and the growth and survival of cancerous cells . IGF‐1R has been implicated in various cancers, including breast and lung cancer . It has been described as a ‘potent transforming and mitogenic agent’.…”

Comment on ‘Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab’

“…We have recently investigated the expression of EMT-related molecules ( Yamashita et al , 2010 ) and IGF-1R ( Nakagawa et al , 2011 ) in NSCLC patients who underwent curative surgery. We have analysed the correlation between EMT molecules and IGF-1R.…”

Alterations of insulin-like growth factor-1 receptor gene copy number and protein expression are common in non-small cell lung cancer

“…One previous study by Dziadziuszko et al 15 demonstrated a favourable prognostic value of high IGF1R GCN but not IGF1R gene expression evaluated by quantitative reverse transcription PCR, or IGF1R protein expression. In another study, lung ADCs with high IGF1R protein expression (cut-off value of 10% positive cells) showed an independent increased risk of postoperative recurrence but not in SCCs or all NSCLC 33. Another study with multivariate analysis showed high expression of IGF1R, and EGFR was a worse prognostic factor of disease-free survival 30…”